Modulation of synaptic efficacy is an important cellular mechanism by which the nervous system can vary its behavioral output in response to different environmental stimuli. Much of our understanding of the mechanisms of such modulation has come from the examination of "simple" nervous systems, in particular the central nervous systems of gastropod molluscs. It has been difficult thus far to apply similar analyses to study the direct effects of neuromodulators on the effector organs in such organisms and thus, to compare the role of central and peripheral modulation by neurotransmitters on the functioning of these effector systems. In contrast to other molluscan effector systems, the salivary neuroeffector complex of Helisoma is a system in which both the central and peripheral components are readily accessible to intracellular analysis. This study proposes to utilize the particular advantages of this system to examine the ionic mechanisms involved in the modulation of the synapse between the identified presynaptic neuron (buccal neuron 4) and the cells in the salivary gland. The first experiments will be directed towards providing further evidence for the role of acetylcholine as a neurotransmitter at this synapse. Subsequently the neurotransmitters which modulate the efficacy of this synapse will be identified. The ionic basis of the plateau phase of the neuron 4 action potential and the relationship between the size of the psp in the salivary cells and the duration of the neuron 4 action potential and soma membrane potential will be determined by voltage clamping the soma of neuron 4. The ionic mechanisms involved in the modulation of the neuron 4 action potential by the neurotransmitters previously identified will be characterized. The ionic basis of the action potential in the salivary cells will also be characterized using a single-electrode voltage clamp. Finally, the ionic mechanisms involved in the modulation of the electrical activity of the salivary cells by the previously identified neurotransmittes will be characterized. These studies will provide the first detailed analysis of neuromodulatory mechanisms affecting synaptic transmission at a peripheral synapse.